AB0146 BAFF, APRIL y BAFFR: DIFFERENTIAL BIOMARKERS BETWEEN IgA VASCULITIS AND IgA NEPHROPATHY?
Authors: D. Prieto-Peña, F. Genre, S. Remuzgo Martinez, V. Pulito-Cueto, B. Atienza-Mateo, B. Sevilla, J. Llorca, N. Ortego, M. Leonardo, A. Peñalba, L. Martín-Penagos, J. A. Miranda Fillloy, J. Narváez, L. Caminal Montero, P. Collado, A. Fernandez-Nebro, G. Díaz-Cordoves, S. Cigarrán, J. Calviño, C. Cobelo, D. De Argila, E. F. Vicente-Rabaneda, E. Rubio-Romero, M. Leon Luque, J. M. Blanco-Madrigal, E. Galíndez-Agirregoikoa, O. Gualillo, J. Martin Ibanez, S. Castañeda, R. Blanco, M. A. González-Gay, R. López-Mejías
Journal: Annals of the Rheumatic Diseases (2022)

Background IgA vasculitis (IgAV) and IgA nephropathy (IgAN) are inflammatory conditions [1, 2], that share pathogenic mechanisms [1], in which B-lymphocytes are described as key cells implicated in these processes. BAFF, APRIL and BAFF-R are cytokines implicated in the development of B-lymphocytes [3, 4] and in autoimmune processes [5, 6]. In this regard, an influence of BAFF, APRIL and BAFFR polymorphisms was observed on several immune-mediated conditions, being BAFF GCTGT&gt;A a shared insertion-deletion variant for inflammatory conditions [7, 8]. Objectives To determine whether BAFF, APRIL and BAFFR could be used as differential biomarkers between IgAV and IgAN. Methods BAFF rs374039502 (which colocalizes with BAFF GCTGT&gt;A), two tag variants within APRIL (rs11552708 and rs6608) and two tag variants within BAFFR (rs7290134 and rs77874543) were genotyped in 394 Caucasian IgAV patients, 95 patients with IgAN and 832 matched healthy controls. Results Similar genotype and allele frequencies were observed in the whole cohort of patients with IgAV when compared to those with IgAN when BAFF, APRIL and BAFFR variants were analyzed independently (Table 1). In accordance with that, no BAFF, APRIL and BAFFR genotype or allele differences were detected between IgAV patients who developed nephritis and patients with IgAN (Table 1). Additionally, no statistically significant differences were observed between the whole cohort of patients with IgAV and healthy controls as well as between patients with IgAN and healthy controls when each when BAFF, APRIL and BAFFR genetic variant was also analyzed independently (Table 1). Similar results were disclosed when haplotype frequencies of APRIL and BAFFR were compared between the different comparative groups above mentioned (data not shown). Table 1. Genotype and allele frequencies of BAFF, APRIL and BAFFR in the whole cohort of patients with IgAV, patients with IgAV who developed nephritis, patients with IgAN and healthy controls. Polymorphism Change Data set Genotypes, % (n) Alleles, % (n) 1/2 1/1 1/2 2/2 1 2 BAFF rs374039502 T/A IgAV 92.1 (363) 7.9 (31) 0.0 96.1 (757) 3.9 (31) IgAV with nephritis 90.1 (128) 9.9 (14) 0.0 95.1 (270) 4.9 (14) IgAN 91.6 (87) 8.4 (8) 0.0 95.8 (182) 4.2 (8) Controls 91.8 (764) 7.8 (65) 0.4 (3) 95.7 (1593) 4.3 (71) APRIL rs11552708 G/A IgAV 78.7 (310) 20.1 (79) 1.3 (5) 88.7 (699) 11.3 (89) IgAV with nephritis 81.1 (116) 18.9 (27) 0.0 90.6 (259) 9.4 (27) IgAN 75.8 (72) 23.2 (22) 1.1 (1) 87.4 (166) 12.6 (24) Controls 78.7 (655) 19.7 (164) 1.6 (13) 88.6 (1474) 11.4 (190) APRIL rs6608 C/T IgAV 72.6 (286) 25.4 (100) 2.0 (8) 85.3 (672) 14.7 (116) IgAV with nephritis 75.5 (108) 23.1 (33) 1.4 (2) 87.1 (249) 12.9 (37) IgAN 65.3 (62) 30.5 (29) 4.2 (4) 80.5 (153) 19.5 (37) Controls 71.0 (591) 26.6 (221) 2.4 (20) 84.3 (1403) 15.7 (261) BAFFR rs7290134 A/G IgAV 58.9 (232) 35.5 (140) 5.6 (22) 76.6 (604) 23.4 (184) IgAV with nephritis 60.1 (86) 32.2 (46) 7.7 (11) 76.2 (218) 23.8 (68) IgAN 57.9 (55) 38.9 (37) 3.2 (3) 77.4 (147) 22.6 (43) Controls 58.7 (488) 35.1 (292) 6.3 (52) 76.2 (1268) 23.8 (396) BAFFR rs77874543 G/C IgAV 83.2 (328) 15.5 (61) 1.3 (5) 91.0 (717) 9.0 (71) IgAV with nephritis 83.1 (118) 16.9 (24) 0.0 91.5 (260) 8.5 (24) IgAN 86.3 (82) 13.7 (13) 0.0 93.2 (167) 6.8 (13) Controls 83.7 (696) 16.0 (133) 0.4 (3) 91.6 (1525) 8.4 (139) IgAV: IgA vasculitis; IgAN: IgA nephropathy. Conclusion Our results reveal a similar BAFF, APRIL and BAFFR genetic distribution in IgAV and IgAN, suggesting that these genes could not be used as differential biomarkers between these pathologies. References [1] N Engl J Med 2013;368:2402-14 ; [2] Am J Kidney Dis 1988;12:373-7; [3] J Exp Med 1999;189:1747-56 ; [4] Nat Genet 2005;37:793-4; [5] Arthritis Res Ther 2018;20:158 ; [6] Arthritis Res Ther 2020;22:157; [7] Engl J Med 2017;376:1615-26 ; [8] Sci Rep 2018;8:8195 . Acknowledgements This study was supported by the European Regional Development Fund (ERDF) and “Fondo de Investigaciones Sanitarias” (grant PI18/00042 and PI21/00042) from ‘Instituto de Salud Carlos III’ (ISCIII, Health Ministry, Spain). DP-P is a recipient of a Río Hortega programme fellowship from the ISCIII, co-funded by the European Social Fund (ESF, `Investing in your future´) [grant number CM20/00006]; SR-M is supported by funds of the RETICS Program co-funded by ERDF [grant number RD16/0012/0009]; VP-C is supported by a pre-doctoral grant from IDIVAL [grant number PREVAL 18/01]; RL-M is a recipient of a Miguel Servet type II programme fellowship from the ISCIII, co-funded by ESF `Investing in your future´ [grant number CPII21/00004]. Disclosure of Interests Diana Prieto-Peña: None declared, Fernanda Genre: None declared, Sara Remuzgo Martinez: None declared, Verónica Pulito-Cueto: None declared, Belén Atienza-Mateo: None declared, Belén Sevilla: None declared, Javier Llorca: None declared, Norberto Ortego: None declared, Maite Leonardo: None declared, Ana Peñalba: None declared, Luis Martín-Penagos: None declared, Jose Alberto Miranda Fillloy: None declared, J. Narváez: None declared, LUIS CAMINAL MONTERO: None declared, PAZ COLLADO: None declared, Antonio Fernandez-Nebro: None declared, Gisela Díaz-Cordoves: None declared, Secundino Cigarrán: None declared, Jesús Calviño: None declared, Carmen Cobelo: None declared, Diego de Argila: None declared, Esther F. Vicente-Rabaneda: None declared, Esteban Rubio-Romero: None declared, MANUEL LEON LUQUE: None declared, Juan María Blanco-Madrigal: None declared, E. Galíndez-Agirregoikoa: None declared, Oreste Gualillo: None declared, Javier Martin Ibanez: None declared, Santos Castañeda: None declared, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Grant/research support from: Abbvie, MSD and Roche, Miguel A González-Gay Speakers bureau: Abbvie, MSD, Jansen, and Roche, Grant/research support from: Abbvie, Pfizer, Roche, Sanofi, Lilly, Celgene, MSD and GSK, Raquel López-Mejías: None declared